Immune evasion mechanisms in colorectal cancer liver metastasis patients vaccinated with TroVax (MVA-5T4)

  • Eyad Elkord
  • Adam Dangoor
  • Deborah J. Burt
  • Thomas D. Southgate
  • Sai Daayana
  • Richard Harrop
  • Jan W. Drijfhout
  • David Sherlock
  • Robert E. Hawkins
  • Peter L. Stern
Original Article

Abstract

We have recently reported the results of a phase II trial in which two TroVax [modified vaccinia ankara (MVA) encoding the tumour antigen 5T4] vaccinations were given to patients both pre- and post-surgical resection of liver metastases secondary to colorectal cancer (CRC). 5T4-specific cellular responses were assessed at the entry and 2 weeks after each vaccination by proliferation of fresh lymphocytes and ELISA for antibody responses; 18 from the 19 CRC patients mounted a 5T4-specific cellular and/or humoral response. Here, we present a comparison of individual and between patient responses over the course of the treatments using cryopreserved peripheral blood mononuclear cells (PBMC) samples from the baseline until after the fourth vaccination at 14 weeks. Assays used were proliferation assay with 5T4-Fc fusion protein, overlapping 32mer 5T4 peptides, MVA-LacZ and MVA-5T4 infected autologous monocytes. Responses to 5T4 protein or one or more peptide pools were pre-existing in 12/20 patients and subsequently 10 and 12 patients showed boosted and/or de novo responses, respectively. Cumulatively, 13/20 patients showed proliferative responses by week 14. We also assessed the levels of systemic T regulatory cells, plasma cytokine levels, phenotype of tumour-infiltrating lymphocytes including T regulatory cells and tumour HLA class I loss of expression. More than half of the patients showed phenotypes consistent with relative immune suppression and/or escape highlighting the complexity of positive and negative factors challenging any simple correlation with clinical outcome.

Keywords

Colorecta cancer 5T4 TroVax Immune evasion T regulatory cell 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Eyad Elkord
    • 1
    • 2
    • 6
  • Adam Dangoor
    • 1
    • 2
  • Deborah J. Burt
    • 1
  • Thomas D. Southgate
    • 1
  • Sai Daayana
    • 1
  • Richard Harrop
    • 4
  • Jan W. Drijfhout
    • 3
  • David Sherlock
    • 5
  • Robert E. Hawkins
    • 2
  • Peter L. Stern
    • 1
  1. 1.CR UK Immunology Group, Paterson Institute for Cancer ResearchUniversity of Manchester, Christie Hospital NHS TrustManchesterUK
  2. 2.Department of Medical OncologyUniversity of Manchester, Christie Hospital NHS TrustManchesterUK
  3. 3.Department of Immunohematology and Blood TransfusionLeiden University Medical CentreLeidenNetherlands
  4. 4.Oxford BioMedica, Medawar CentreOxfordUK
  5. 5.Department of SurgeryNorth Manchester Healthcare NHS TrustManchesterUK
  6. 6.Cellular Immunology SectionLaboratory of Immunology, National Institutes of HealthBethesdaUSA

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